Topical aminocaproic acid in the treatment of traumatic hyphema.

OBJECTIVES: To determine whether topically applied aminocaproic acid, like systemic aminocaproic acid, effectively reduces secondary hemorrhage after hyphemas and to compare the safety and effectiveness of topical application with those of systemic use and a control group. DESIGN: A prospective, randomized, double-masked, multicenter study. PATIENTS: Sixty-four patients with traumatic hyphema treated with topical or systemic aminocaproic acid and compared with 54 control patients with hyphema. Daily slitlamp examinations for hyphema grading and corneal clarity, initial and final visual acuity, applanation tonometry, and fundus indirect ophthalmoscopy were studied. Follow-up was 6 months to 5 1/2 years (mean, 2.96 years). RESULTS: Compared with the control group, topical and systemic aminocaproic acid was statistically significant in preventing secondary hemorrhage. Only 3% (2/64) of the patients who received topical or systemic aminocaproic acid had secondary hemorrhage compared with 22% (12/54) of the control group (P = .002). Final visual acuity was 20/40 or better in 30 patients (86%) in the topical group compared with 23 patients (43%) in the control group (P < .001). Final visual acuity was 20/40 or better in 20 patients (69%) in the systemic aminocaproic acid group compared with 23 patients (43%) in the control group (P = .04). The topical aminocaproic acid group had a final visual acuity of 20/40 or better in 86% of patients, compared with 69% of patients in the systemic group. CONCLUSIONS: Topical aminocaproic acid appears to be a safe, effective treatment to prevent secondary hemorrhage in traumatic hyphema. It is as effective as systemic aminocaproic acid in reducing secondary hemorrhage. No systemic side effects were observed with topical use. Topical aminocaproic acid provides an effective out-patient treatment for traumatic hyphemas.

Variable inhibition of cell-free translation by HIV-1 transcript leader sequences.

The 5' ends of all human immunodeficiency virus type I (HIV-1) transcripts have the potential to coordinately regulate translation of HIV-1 mRNAs. Conflicting observations of the translational impact of these sequences in various systems stimulated these analyses of translation in reticulocyte lysates. We report a sensitive, rapid, quantitative, and inexpensive cell-free translation assay in which translational efficiency is monitored by enzymatic assay of the translation products. Using this assay and conventional radiolabeling assays, we demonstrate that the HIV-1 transcript leader inhibits downstream translation and that the stem-loop structure is required. Under our assay conditions, this inhibition occurs predominantly in cis and is not mediated by the 68 kD, interferon-induced, double-stranded RNA-activated kinase (p68). However, under other assay conditions the HIV-1 leader may activate p68 and inhibit translation in trans. We show that variation between individual preparations of cell-free extracts can dramatically alter the magnitude of the translational inhibition by the HIV-1 leader. Further, we provide evidence that a heat-labile factor is required for efficient translation of transcripts containing the HIV-1 leader. These observations provide a foundation for identifying factors required for translation of HIV-1 transcripts.

Early postimplantation embryolethality in mice following in utero inhibition of adenosine deaminase with 2'-deoxycoformycin.

Adenosine deaminase (ADA) catalyzes the hydrolytic deamination of adenosine (or 2'-deoxyadenosine) to inosine (or 2'-deoxyinosine). Previously, we have shown that ADA activity is subject to strong cell-specific developmental regulation in placental tissues of mice between days 6 and 11 of gestation (Knudsen et al.:Biology of Reproduction 39:937-951, 1988). In the present study, we examined the effects of intrauterine exposure to 2'-deoxycoformycin (dCF; pentostatin), a potent irreversible inhibitor of ADA, on early postimplantation development. Deoxycoformycin was administered to pregnant ICR mice as a single intraperitoneal injection at a dose of 5 mg/kg on one of days 6 through 11 of gestation (plug day 0). A marked increase in the incidence of implantation site resorptions was observed following treatment specifically on days 7 (61% resorbed) or 8 (78% resorbed). No effect was observed following treatment on days 6, 9, 10, or 11. ADA-immunoreactive protein was shown, by ABC-immunoperoxidase staining on days 7 or 8 of gestation, to be present at high levels in decidual cells of the antimesometrial region but at below-detectable levels in the embryo. Treatment of pregnant dams with dCF on day 7 produced a complete (greater than 99%) inhibition of ADA activity in the antimesometrial decidua by 30 min, induced excessive cell death in the prospective neural plate and primary mesenchyme of the trilaminar disc by 6 h, and arrested embryonic development at an early somite stage. These results suggest that the antimesometrial decidua plays a protective role in preventing an inappropriate accumulation of endogenous ADA substrates in the implantation site.